Download 1 Candidiasis: predisposing factors, prevention, diagnosis and

Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment
Natália Martinsa,b, Isabel C.F.R. Ferreiraa,* Lillian Barrosa, Sónia Silvab, Mariana
Henriquesb,*
a
Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus
de Santa Apolónia, Apartado 1172, 5301-855 Bragança, Portugal.
b
IBB - Institute for Biotechnology and Bioengineering, Centre of Biological
Engineering, University of Minho, 4710-057 Braga, Portugal.
Authors to whom correspondence should be addressed (e-mail: [email protected],
telephone +351273303219, fax +351273325405; e-mail: [email protected],
telephone +351253604401, fax +351253604429).
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SUMMARY
Candidiasis is the most common opportunistic yeast infection. Candida species and
other microorganisms are involved in this complicated fungal infection, but Candida
albicans continues to be the most prevalent. In the past two decades, it has been
observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts,
not only in immunocompromised patients, but also related to nosocomial infections and
even in healthy individuals. There is a widely variety of causal factors that contribute to
yeast infection which means that candidiasis is a good example of a multifactorial
syndrome. Due to rapid increase in the incidence of these infections, this is the subject
of numerous studies. Recently, the focus of attention is the treatment and, above all, the
prevention of those complications. The diagnosis of candidiasis could become quite
complicated. Prevention is the most effective “treatment”, much more than eradication
of the yeast with antifungal agents. There are several aspects to consider in the daily
routine that can provide a strength protection. However, a therapeutic approach is
necessary when the infection is established and, therefore, other alternatives should be
explored. This review provides an overview on predisposition factors, prevention and
diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.
Keywords: Candidiasis; predisposing factors; diagnosis; prevention; alternative
treatment; therapeutic approach
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1. Introduction
Candida species are involved in the main opportunistic yeast infection in the world,
candidiasis, but among the species of the genus, Candida albicans continues to be the
most common. Although this yeast is responsible for approximately 50-90% of human
candidiasis, C. albicans is part of the commensal flora of more than half of the healthy
population. Colonization by this yeast is beneficial to the host, because not only limits
the growth of other opportunistic pathogenic fungi, but also promotes the functioning of
the immune system [1–5].
In the last two decades, it has been observed a considerable increase in the incidence of
deep fungal infections, not only in immunocompromised patients, but also related to
nosocomial infections, and even in healthy population [4,6–15]. Thus, with the
increased incidence of deep fungal infections (chronic candidiasis), the primitive idea
that they were related to a restrict number of pathogenic fungi and specific geographical
area was completely changed. Furthermore, with the rapid increase of candidiasis
incidence, other Candida species and microorganisms besides C. albicans, have been
involved in such infections [2,5,6,16–18]. The balance between C. albicans and nonCandida albicans Candida (NCAC) species determine the profiles associated with
virulence. So, the most common species are C. albicans, C. tropicalis, C. glabrata, C.
dubliniensis, C. parapsilosis, C. orthopsilosis, C. metapsilosis, C. krusei, C. famata, C.
guilliermondii and C. lusitaniae. Other relevant fact associated with virulence is their
capacity to form biofilms with other species, which together with the presence of
teleomorph forms (sexual phase of fungi in which the same biologic entity could have
two different scientific names), difficult the treatment and alter the susceptibility
profiles to traditional antifungals agents [3,9,10,13,19–22].
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Although biofilm formation lead to an increase in the persistence and resistance to
antifungals, other factors, like adaptation to the pH level, adherence of yeast cells to the
host cells, proteolytic enzymes, phenotypic switching, and morphological transition
(ability of yeast to change morphologically from blastoconidia to pseudohyphae and
hyphae), affect the strategies to prevent and treat this pathogenic infection. Despite C.
albicans is still the focus of a wide range of studies, some researches have been
demonstrated a significant increasing of infections caused by NCAC species. There are
some associated factors with the virulence. The presence of hemolytic exoenzymes is
very important because it allows an acquisition of iron ions from hemoglobin, by yeasts.
Moreover, there is a positive correlation between this metal and the establishment and
dissemination of infections. The metabolic activity and the capacity of biofilm
formation also appear like important correlating factors of pathogenicity, once they
interfere in the level of virulence expression and in the level of resistance to antifungal
agents. A high metabolic activity of NCAC species was demonstrated, which could be a
cause of the increasing frequency of fungal infections related to these yeasts, including
the possibility of systemic infections. According to these facts, it was possible to
demonstrate the complexity of the epidemiological chain of colonization – infection
processes. Like expression of virulence-associated factors are strain dependent, an
accurate identification of yeasts and their virulence-associated factors is essential to
detect the emergence of yeasts and to predict the antifungal agents response,
considering the increasing tolerance and antifungal resistance mechanisms [1,2,20,22–
24].
Due to the increasing evidence of antimicrobials and antifungals resistance, several
studies have been developed towards the identification and evaluation of efficient
alternative therapeutics. Natural products, in particular, those from plants, have been
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explored with that purpose; the therapeutic potential of phytochemicals, the synergistic
effects among them and the related mechanisms of action have been extensively studied
[25–35]. Nevertheless, many extracts/compounds from plant origin remain unknown
and could constitute an alternative or complementary treatment for candidiasis.
Considering all the stated, candidiasis is indeed much more than C. albicans overgrowth
and, therefore, the most relevant topics involved in this fungal infection are presented
and discussed in the present manuscript, namely: description of candidiasis and their
main classes, predisposing factors, diagnosis (signals, symptoms and methods),
prevention and alternative treatment (diet and nutrition, enhancing immunity system,
detoxification, natural anti-yeast agents and therapeutical approach) (Figure 1).
2. Description of candidiasis and main classes
Yeasts are part of the commensal fungi flora of the healthy population. However, with
the significant and rapid increase in the incidence of opportunistic fungal infections, the
focus of attention has been the treatment and, above all, prevention of those
complications. Although other fungi species are involved in nosocomial infections, like
Aspergillus spp., Zygomyces spp., Fusarium spp., Scedosporium spp., Cryptococcus
spp., Trichosporon spp., Geotrichum spp., and Rhodotorula spp., C. albicans continues
to be the most prevalent, counting to 50-90% of the isolates from fungal infections
[1,9,10,22,36,37].
Candida albicans is a common species in genitourinary and gastrointestinal tracts of
healthy people, but it is also able to cause problems, mainly vaginal infections in
woman. This microorganism is responsible for mouth and mucocutaneous infections.
However, it has been frequently observed an evolution to chronic forms, generating
complicated infections, such as septicemia, endocarditis, meningitis, and peritonitis,
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especially in patients with reduced immune function or taking antibiotic therapies.
Some reports described that oral candidiasis appeared as early as the 2nd century A.D.
by Galen, who described it as aphthas albus. Other reviews reported that it was not until
the mid-19th century that clinical nature of oral candidiasis was defined and the etiologic
agent identified. Notwithstanding, and despite the other types of mucocutaneous
candidiasis, oral candidiasis is still the most frequent. There has been a wide variety of
synonyms used for the members of genus Candida, 166 synonyms being recognized for
C. albicans worldwide. Actually, there are between 150 and 200 species recognized in
the genus, but only seven Candida species are classified as having major medical
importance, being C. albicans the most important one. Other Candida species like C.
tropicalis, C. glabrata, C. parapsilosis, C. stellatoidea, C. krusei and C. kyfer are
encountered in human infections [2,5,15,38,39].
The increase in the number of organ transplantations, the rise of immunocompromised
individuals and the use of invasive devices (catheters, artificial joints and valves) are a
major factor that contributes to higher patient’s susceptibility to nosocomial infections.
Despite being Candida species the fourth leading cause of hematogenous infections,
these species are not exclusively related to nosocomial infections (candidemia), because
the same infections can also occur in healthy population. There are several classes of
candidiasis, which have become more common in recent years [4,6,13,17,40,41].
Depending on body location, the mucocutaneous candidiasis can be classified as:
genital candidiasis, intrauterine candidiasis, anal candidiasis, nails candidiasis and oral
candidiasis (Figure 1).
2.1. Genital candidiasis
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Vulvovaginal candidiasis (VVC) is the most frequent type of genital yeast infection.
Approximately 75% of women experience, at least once in their lifetime, an episode of
VVC, 40-50% experience at least one additional episode of infection, 20-50% remain
without any clinical manifestation, and lastly, 5% experience recurrent VVC episodes
[9,10,42,43]. Although, not being a threat to life, it is unpleasant and problematic,
causing a variable degree of itching and whitish discharge, abundant and flocculent.
This infection is very common in pregnant women, especially in the last trimester of
pregnancy, when a variation of progesterone, estradiol and glycogen, associated with an
increase in vaginal pH, favors the emergence of these infections. In this case, special
attention should be given due to the potential occurrence of contamination of the fetus
in the uterus, or even the child during childbirth. On the other hand, it has been
observed that, in individuals with diabetes, the incidence of vaginal candidiasis is
higher. Similarly, patients submitted to broad-spectrum of antibiotic therapy, used to
treat bacterial infections, and even the use of oral contraceptives, are also important
factors associated with higher rates of incidence of VVC [42,44–47].
In men, balanitis, which usually appear after sexual contact, is characterized by the
appearance of a rash, more or less prickly, followed by small pustules on rocking
groove-preputial discharge, more or less abundant. Although this kind of injury is well
defined, in particular cases it can extend to the groin and perianal region. The major
factors associated with this type of infections are antibiotic therapies, diabetes and
vaginal secretions of the sexual partner [1,17,48].
2.2. Intrauterine candidiasis
This type of infection is frequent during pregnancy. It is important to avoid the
occurrence of this type of intense vaginitis in the last few weeks of pregnancy, because
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it can complicate and extend to the uterus, infecting the child before birth. At childbirth,
or in the first hours of life, it can be observed a widespread rash, maculopapular or
pustular-vesicular. During the following weeks after birth, the clinical status may be
complicated, extending to other body locations, which usually are treated with local
antibiotics [5,42,43,49].
2.3. Anal candidiasis
This type of infection is characterized by intense itching/pruritus, accompanied by
burning sensation, and localized erythema around the anus. Skin may appear macerated
with circumscribed lesions, which may eventually invade the intergluteal groove [49–
51]. This type of infection is most common in children; despite the frequency in women
due to the use of hormonal contraceptives, intimate hygiene products, clothing and their
practice of oral and anal intercourse, functioning as transient colonization of local
organisms shed from the intestinal tract. As candidiasis can be sexually acquired, males
can be affected, because they may acquire infection from the gastrointestinal tract of
their partners. However, in some cases, the factors causing that condition are still
unknown, but seems that the main problem of this pathogenesis are secondary infections
caused by aerobic and facultative anaerobes microorganisms, such as Staphylococcus
spp., Streptococcus spp. and Escherichia coli [48,50–52].
2.4. Nails candidiasis
Candida species are not considered normal yeasts on nails flora. Therefore, this type of
infection is a sign of colonization (secondary growth) despite primary infections of nail
fold and nail bed with Candida species may also occur, which are related to a disease of
the nails. Onyxisdystrophy or periungal tissue is related to nail disease. This type of
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infection may appear, like paronychia and onychia. The paronychia is characterized by
an inflammation, more or less painful, in peripheral skin nail, which appears red and
brilliant. The predisposing factors are essentially, sex, different traumas (e.g., in
manicure), professional activity and hormonal variations. Although infrequent in males,
this infection can appear in cooks, confectioners and employees of canning factories
[1,17,49].
Usually, the nail injury itself, or onyxis (ingrown nail), is secondary to paronychia. It is
characterized by a progressive striation, dyschromias (discoloration) and opacity of the
nail plate, which ultimately becomes crumbly. This infection appears abruptly and
painfully, leading to detachment of the nail and can spread to other nails. Still, it can be
observed fungal colonization in interdigital areas, by Candida species, commonly
known as digital intertriginous. Preferentially, it is located in the hands and between the
ring and middle fingers, although it can also appear in the corners of the fingers. It is
commonly associated with professions or occupations in which there is a frequent
contact with water. The injury erythema-scaly, itchy and exudative generally is well
delimited peripherally and the epidermis appears detached. It is less frequent in feet, but
can reach one or more commissures of fingers [1,17,49,50].
Intertriginous can still be located at the level of the submammary, mainly in obese
women, suprapubic fold, groin and intergluteal cleft. It is characterized by the
appearance of small vesicles and pustules which, by breakage, give rise to exudative red
spots [1].
2.5. Oral candidiasis
Oral and perioral candidiasis is the more common type of acute mucocutaneous
candidiasis. It is characterized by the appearance of small spots or whitish papules on
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the tongue, inside the cheeks and in the palate, forming a creamy and very adherent
layer mucosa. In some cases, it may extend up and cover the tongue, palate and
pharynx, but also corners of the mouth could be reached. When this happens, it is
labeled as angular cheilitis, being evidently a mucosal thickening and cracking. This
type of candidiasis particularly affects people with immune system disorders and people
with dental prostheses. It can be also found in patients receiving chemotherapy for
cancer treatment, or taking immunosuppressive drugs to protect transplanted organs or
in patients infected by HIV. In children and young people, it may be involved with oral
("thrush") and lingual disease. In addition, and despite being very rare, esophageal
candidiasis can occur in patients infected by HIV and cancer [2,5,40,53–55].
3. Predisposing factors
Although Candida species is commensal to human organism and virtually present in
healthy people, in the past two decades, an abnormal overgrowth in the gastrointestinal
(GI), urinary and respiratory tracts has been observed [2,3,6,10,56]. During some days
after childbirth, that species colonize the mucosa of GI tract (40-50%) and upper
respiratory passages, as well as the mouth, pharynx and larynx. Normally, C. albicans
lives smoothly in the inner warm creases and crevices of the GI tract (and vaginal tract
in women). During pregnancy, Candida species colonization increases 30-40%,
depending upon altered immune response, bacterial flora, positive variations of
glycogen and pH levels; however, mostly during the normal life cycle, other factors can
affect, such as hygiene and oral contraceptive use, which contributes to 5-30% of the
infections. In men, up to 10% of these species are found on the genitalia, in the
transitional zone, between the mucous membrane and the skin [1,13,18,40,44,46]. The
overgrowth of C. albicans is an important cause of a wide variety of symptoms that
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affect directly the wellbeing of individuals, therefore there is an urgent need to
recognize candidiasis as a complex medical syndrome and evaluate the magnitude of the
problem regarding prevention, which passes through the control of risk factors.
There are several factors that contribute to yeast infection, which means that
candidiasis, and more especially chronic candidiasis, is a good example of a
multifactorial syndrome. In the next steps the major and most important factors are
explained namely, decreased digestive secretions, dietary factors, nutrients deficiency,
impaired immune system and underlying disease states, impaired liver function, drugs
and prolonged use of antibiotics, and altered bowel flora (Figure 1).
3.1. Decreased digestive secretions
In a normal organism the digestive secretions, such as hydrochloric acid, bile and
pancreatic enzymes have an important role not only for a correct digestion, but also to
prevent Candida overgrowth and its penetration into absorptive surfaces in the GI tract.
Therefore, an improvement of digestive secretions is pivotal and, in some cases, is an
important step to treat chronic candidiasis.
Pancreatic enzymes perform an important role as therapeutic agents enabling an
efficient and complete digestion of proteins and other dietary compounds. Any
dysfunction on this process leads to several problems, such as food allergies and
formation of toxic substances. Furthermore, those enzymes are responsible for the
preservation of the integrity of small intestine without parasites and other opportunist
microorganisms (bacteria, yeasts, worms, protozoa), helping in the degradation of
immunocomplexes [57,58].
The intake of antacids and antiulcer drugs has a high risk of GI infections, showing a
Candida species overgrowth in the stomach. Therefore, to restore the normal digestive
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secretions to proper levels, through the use of supplementary hydrochloric acid,
pancreatic enzymes and substances that promote the normal bile flow, is highly
important in the treatment of chronic candidiasis [57,58].
3.2. Dietary factors and nutrients deficiency
A balanced organism needs all the macro and micronutrients in right proportions and,
therefore, any unbalanced diet affects the wellbeing of the body and potentiates growing
and colonization of certain invaders. Some foods, like refined sugars, sucrose, fruit
juice, honey and maple syrup have an important interference, functioning like growth
enhancers. Moreover, foods with high content of yeast and fungi favor the growth of
Candida; some examples are cheeses, alcoholic beverages and dried fruits. Another
food group that stimulates growth is milk and dairy products, not only because of the
high content of lactose but also, in some cases, due to the presence of antibiotics.
Another important situation observed in most individuals with chronic candidiasis, is
the presence of food allergies, therefore all known allergens should be eliminated
[40,42,55,57,59–61]. Thus, dietary factors should be monitored according to the needs
of each individual.
Some essential nutrients usually in deficit on chronic candidiasis are zinc, magnesium,
selenium, essential fatty acids, folic acid and vitamins B6 and A [57,59,60,62].
Furthermore, iron has been considered as an essential micronutrient rather than a
supplement, and there are several recent studies that indicate its important role in
fostering and colonization by microorganisms, including Candida and other yeasts
[9,42,63–66].
3.3. Impaired immune system and underlying disease states
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Dysfunctions of the immune system turn the human body more vulnerable to various
kinds of infections. Thus, it is of extreme importance to maintain the good conditions of
the immune system in order to prevent overgrowth of certain microorganisms and
opportunistic infections. By itself, a weak immune system is already sufficient to
constrain the health and resistance of individuals, although with the current and
prolonged/frequent consumption of antibiotics, chemotherapy, steroids, radiation, stress,
as well as some environmental contaminants, the body is still more susceptible.
Furthermore, any disease that, directly or indirectly, affects the immune system
increases the body's susceptibility to the growth and development of pathogenic and
opportunistic microorganisms. This is the case of some increasing prevalence diseases,
such as cancer, diabetes, and hypothyroidism, that in addition to debilitate immune
system of individuals, has led to a continuous and exacerbated prescription of
immunosuppressant drugs [1,11,17,18,24,37,40,41,67–69].
In fact, the most common diseases that predispose to an increased sensitivity to C.
albicans overgrowth are diabetes mellitus, cancer, leukemia, AIDS, thyroid dysfunction
and other diseases, in which host defense mechanisms are suppressed or adrenal cortex
steroids/antibiotics/other similar drugs are used (immunosuppressed patients)
[6,10,12,24,25,37,40,53,56,70–72].
3.4. Impaired liver function
The modifications of the liver functions, as a result of injury or chemical causes, can
change detoxification mechanisms. In this situation, as the liver is not able to perform
its functions properly, toxins are absorbed by the intestine being accumulated, which
affects more the liver and other organs function, and increase the body's sensitivity to
chemicals. The accumulation of toxins in the body, as a result of liver damage,
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associated with changes in the mechanisms of detoxification, also stimulates C. albicans
overgrowth. One way to diagnose if liver function is affected or if the mechanism of
filtration of the blood is not properly being done, is through the manifestation of
symptoms (e.g., psoriasis, premenstrual syndrome, among others) of chronic candidiasis
outside of digestive tract [57,60,73,74].
3.5. Drugs and prolonged use of antibiotics
Antibiotics have been identified as a major responsible factor for the development of
chronic candidiasis. Since its mode of action is based on the elimination of intestinal
bacteria, responsible for preventing the growth of yeasts and other pathogenic
organisms, as well as suppressing the immune system, antibiotics action result in a C.
albicans overgrowth. This situation becomes shortly a vicious cycle: a person with an
alteration of the immune system is more susceptible to infections and, consequently,
more infections will appear – increasing the doses and frequency in the consumption of
antibiotics. This fact not only favors the overgrowth of C. albicans and other yeasts, but
particularly bacteria, which increasingly develop mechanisms of resistance against
antibiotics [6,17,42,57,69].
An established fact is that, the indiscriminate use of antibiotics substantially increases
the risk of developing complications caused by C. albicans and other resistant
pathogens. This is particularly important in hospitals because nosocomial infections by
resistant microorganisms often lead to lethal complications. Therefore, the reduction of
the prescription and use of antibiotics can be considered an effective alternative to
control and/or minimize the resistance problem. Another alarming factor is the
widespread use of antibiotics in animals, which not only contribute to microbial
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resistance in animals themselves, but also indirectly affect humans: antibiotic resistance
and consumption of food contaminated by antibiotics [1,6,17,23,40,42,43,46,70,75,76].
The increasing incidence of Crohn’s disease and other inflammatory bowel diseases,
which previously were only prevalent in populations with a strong genetic component,
is also an important factor [77–86].
Other drugs that could favor C. albicans overgrowth are corticosteroids, oral
contraceptives and anti-ulcer drugs. It should be emphasized that individuals who take
anti-ulcer drugs, like ranitidine and cimetidine, may develop C. albicans in the stomach
[6,7,40,42,43,46].
3.6. Altered bowel flora
As described, drugs and other chemical compounds greatly affect the wellbeing of the
body. If the liver does not work properly, products and metabolites resulting from poor
digestion are accumulated in the body causing toxicity and, at the same time, favoring
pathogenic strains, and also C. albicans overgrowth. Therefore, intestinal flora is of
utmost importance in maintaining proper intestinal health and balance, being involved
in the maintenance of nutritional status, immune system function, cholesterol
metabolism, carcinogenic agents and aging. It is imperative to promote healthy and
growth of beneficial intestinal flora, not only after taking antibiotics, but also in other
situations. It should also be noted that chronic stress greatly affects the balance of
intestinal flora and suppresses the immune system function. In other hand, especially in
women, the hormonal balance is very important and the oral routine of contraceptive
use is itself a predisposing factor to C. albicans overgrowth once it is a causative agent
of variation in the balance of the intestinal microflora [1,6,9,23,40,42,46,87,88].
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4. Diagnosis
In some cases, the diagnosis of candidiasis becomes quite complicated and difficult to
establish, since the patients present different signals and symptoms according to age,
gender, host resistance and exposure to environmental factors. Nevertheless, some tools
could be used to screen and determine the presence of yeast infections (diagnosis)
namely, questionnaire, comprehensive digestive stool analysis (CDSA) and laboratorial
techniques (Figure 1).
4.1. Signals and symptoms
Despite fungi and other microbials being widespread in the environment, the systemic
infections thrive very slowly. Most of the times, the individual infected does not have
symptoms or visible signals. According to some authors, namely, oral candidiasis is
classified considering the following aspects: duration (acute or chronic), clinical
features, like color (erythematous/atrophic), location (median rhomboid glossitis,
denture stomatitis, multifocal candidiasis, angular cheilitis), presence of skin lesions, as
well as oral lesions (mucocutaneous), and association with an immunocompromised
host (HIV associated). Other clinical aspects included hyperplastic or hypertrophic
appearance, characterized by papillary hyperplasia of the palate, candida leukoplakia
and hyperplastic median rhomboid glossitis [1,5,17,48,49,57,59,60].
In a more developed stage of infection, a simple sensation of flu or constipation could
occur, like cough or fever, chest pain, chills, weight loss or breathing difficulties.
However, the type and the intensity of signals and symptoms depend on the type and
location of the infection. One of the major explanations for yeasts overgrowth is that the
immune system mechanisms are depleted, or the normal lining of the intestinal tract is
damaged. When this happens, the body can absorb yeast cells, particles of yeast cells, a
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wide of toxins and other substances, resulting in the development of yeast syndrome
[5,49,62].
The major symptoms of patients with yeast infection are divided in different categories,
which are described below. General symptoms include chronic fatigue, loss of energy,
general malaise, and decreased libido. Other category includes gastrointestinal
symptoms, like thrush, bloating, gas, intestinal cramps, rectal itching, and altered bowel
function. In genitourinary system, the major complaints are vaginal yeast infection and
frequent bladder infections. Depression, irritability and inability to concentrate are the
general complaints of nervous system. The occurrence of allergies, chemical
sensitivities and low immune function are also very frequent. A great majority of
patients has shown, in the past history, one or more of these conditions: chronic vaginal
yeast infections; chronic antibiotic use for infections or acne; oral birth control and oral
steroid hormone usage, as well as premenstrual syndrome; sensibility to foods,
chemicals and other allergens; endocrine disturbances; eczema; psoriasis; irritable
bowel syndrome. One of the most important aspects is that most patients have craving
for foods rich in carbohydrates or yeast [1,5,49,62].
Occasionally, patients saying that “feel sick all over” characterize the syndrome. It is
important to consider that women patients have eight times more yeast infections
compared to men, due to the effects of estrogen, birth control pills and the large number
of antibiotics prescriptions [1,5,49,62].
4.2. Diagnosis methods
4.2.1. Questionnaire
C. albicans questionnaire is one of the most useful screening methods to determine and
understand the likelihood of yeast-related illness. It is composed by three sections:
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anamnesis, main symptoms and other symptoms. The complete evaluation is made by
the sum of those sections, directing the treatment and establishing hierarchy of
intervention. Although Candida questionnaire can be profitable, clinical evaluation is
one of the most important and credible methods of diagnosis, including patient’s history
and clinical picture. Promptly, and according to the necessity, laboratory examinations,
like stool cultures for C. albicans and measurement of antibody levels or antigens in the
body, are very useful and accurate [5,43,57].
4.2.2. Comprehensive digestive stool analysis (CDSA)
The stool sample culture exam is very common, but it is inconclusive and provides little
information in the case of active infection. CDSA is an extremely useful and effective
method to determine the existence of some digestive disturbances, functional and
clinical status of the GI tract, which can be one of the major responsible factors of
Candida overgrowth. It also allows determination of the symptoms that are not related
with Candida overgrowth, but associated with the intestinal bacteria overgrowth or
presence of inflammatory bowel disease [57,59,60,62,89].
CDSA is also considered very important to maintain the optimal functioning and
ecology of the GI tract to improve human health and wellness. This noninvasive method
of diagnosis can be considered as an integrated tool. It provides advanced clinical
insight and allows, carefully, an evaluation and examination not only of digestion,
absorption and intestinal capacity or function, but also of intestinal environment, gut
immunology and metabolism, microflora balance and colon risk cancer. Therefore, in
the last instance, it is helpful in the diagnosis and monitorization of disease-specific
infections or conditions, but also determines the etiology of diseases [57,59,60,62,89].
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4.2.3. Laboratorial techniques of diagnostic
Laboratory techniques only confirm the patient's history, physical examination and
CDSA, only few additional data is provided and it is rarely used. However, there are
situations in which the physician or the patients intend to objectify which Candida
species is the main ethiogenic agent. In this case, microbiologic, molecular and
biochemical assays could be used. For example, the blood analysis can be useful, not
only as a method of determination/confirmation, as well as to monitoring therapy. This
test is based on measuring the level of antibodies to Candida antigens. Other
techniques, like urine test, used to measure yeast metabolites and intestinal
permeability, help to assess metabolic reasons for candidiasis [57,59,60,62].
5. Prevention
Considering the facts described above, and being C. albicans a commensal
microorganism and that is present in all people, it is important to control the number
and magnitude of its population. As prevention is the most effective treatment, much
more than the eradication of the yeast with antifungal agents – synthetic or naturals, it is
fundamental to address and amend the predisposing factors. Therefore, maintaining a
good personal hygiene is essential. Moreover, being woman more prone to this kind of
infection, a good vaginal and oral hygiene is essential, in order to reduce the probability
of candidiasis occurrence [5,17,42,46,49,59,60]. Some general guidelines for personal
hygiene are listed in Table 1.
Since deep infections have been increasing, mainly in hospitals, the following aspects
should be considered: probes and catheters should be regularly monitored and removed,
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as soon as possible; and the frequency, duration and amplitude of the quantities of
antibiotics should be kept to a minimum [3,6,9,14,49,72,90].
Not less important, is to avoid certain risk factors, such as diets rich in sugar and poor in
vitamins and minerals, or the use of antibiotics.
6. Alternative treatment
C. albicans is an opportunistic yeast that cause infectious but, in some levels, lives and
grows inside most human bodies. In normal situations, Candida is not harmful because
our bodies are able to keep it under control, mainly by immune cells and probiotic
bacteria. However, some factors previously discussed, like allergies, high-sugar diets,
medications/drugs, and other factors that directly affect the normal balance of intestinal
environment, can kill the friendly bacteria and stimulate the overgrowth of pathogenic
microorganisms [1,68,69,84,87,88]. Therefore, the best complementary treatment is to
reduce and control Candida levels. Several recommendations/interventions are
necessary according to each person. In most of the cases, direct therapy for Candida
species destruction is advantageous, because it assists the body on lowering Candida
species to controllable levels [49,57,59,60]. However, depending on the profile of the
patient, other procedures (diet and nutrition, enhancing immunity system, detoxification
and natural anti-yeast agents; Figure 1) are required and will be discussed.
6.1. Therapeutic considerations
6.1.1. Diet and nutrition
As previously discussed, some dietary factors affect and promote the overgrowth of C.
albicans; therefore, following a special diet for the treatment of candidiasis is crucial.
The most important elements are refined sugars, such as sucrose, fruit juice, honey and
20
other sweet foods, because C. albicans grows in sugar environments. Foods with high
content of fungi or yeasts, like alcoholic beverages, cheeses, dried fruits, bread and
fermented products should be avoided, as also milk and dairy products due to the high
content of lactose and, in some cases, trace levels of antibiotics. Likewise, all the
allergens present in food should be eliminated, since allergies weaken the immune
system, promoting the growth of pathogens. There are several reasons to restrict or
eliminate milk and other dairy products, not only for the high levels of lactose, that
promote Candida overgrowth, but also because it is one of the most frequent food
allergens, and the presence of trace levels of antibiotics disrupt the GI bacterial flora
[42,55,57,59,60,70,87].
Food allergies could be assessed by some immunoanalytical methods, such as ELISA
tests, which determine both IgE- and IgG-mediated food allergies and often help in the
identification of allergies [91–95].
Foods that can be eaten without problems and/or constraints are vegetables, sources of
proteins, such as fish, meat and organic poultry, legumes and whole grains. The latter
consumption is dependent of each individual tolerance. For fruits, although being the
majority alkaline, the recommendation is to eliminate the consumption for a month of
citrus and acidic fruits (e.g., oranges, grapefruit, lemons, tomatoes, pineapple, and
limes); afterwards the consumption can be made twice a week. Apples, cranberries,
cherries, pears and other soft fruits can be daily consumed. Although the existence of
conflicting opinions, the consumption of yogurt containing live probiotic cultures is
recommended in order to replace friendly bacteria. In some cases, for vaginal
candidiasis, a natural unprocessed and unsweetened yogurt can be applied directly into
the vagina or a mixture of one small container of plain yogurt with an equal amount of
water can be used as a douche, once or twice a day, until improvement is observed.
21
Alternatively, or complementary, it is also possible to take supplemental acidophilus or
bifidus, or to open two capsules of acidophilus and add the contents to a douche. It is
also recommended to consume daily oat bran and/or flaxseed, not only as a source of
fiber, being the latter also very effective due to antifungal properties [49,57,59,60].
Table 2 summarizes the most important dietary aspects in fungal infections.
6.1.2. Enhancing immune system
In most cases of chronic candidiasis, the immune system is altered (mostly depressed)
allowing a quick growth of C. albicans. This explains why the patients have repetitive
cycles of infection that lead to increase damages, and further resistance weakening.
Thereby, it is very important to potentiate the immune function, in order to protect the
organism against foreign/opportunist agents. Additionally, in patients suffering from
AIDS or taking immunosuppressive drugs, the immune system is affected, which favors
the C. albicans overgrowth. In both cases, the prevalence of candidiasis is considerable,
being the strength of the immune function very important. In some cases, the debility of
the immune system is related to a decrease in thymus function, represented by an
impairment of cell-mediated immunity [57,59]. There are some points that help to
strength the immune function and that eliminate, suppress or amend the causes of
depressed immune function. The major triggers of impaired immunity and that lead to
C. albicans overgrowth are antibiotics, corticosteroids and other drugs that suppress
immune
system,
as
also
nutrients
deficiency,
food
allergies
and
stress
[1,37,40,53,69,75,80,84].
Accordingly, restoring proper immune function is one of the major objectives in the
treatment of chronic candidiasis; to reach this goal, some strategies could be followed:
stress management, diet restriction, nutritional supplementation, glandular therapy,
22
exercise and the use of plant-based medicines. However, as the clinical remission of
candidiasis is directly dependent on T-cells function, it is also crucial to improve
thymus gland function. To achieve this, it is necessary to guarantee an adequate intake
of antioxidants, through nutritional supplementation, such as carotenes, vitamins A, C
and E, zinc and selenium. Some plants could be used to complement this intervention
namely, Echinacea angustifolia, Hydrastis canadensis and Glycyrrhiza glabra
[49,57,59,62,96].
6.1.3. Detoxification
The human body is continuously exposed to substances and toxic agents, which
accumulates in the body. Therefore, the body detoxification process is continuous,
being widely recognized that different substances (e.g., heavy metals, pesticides,
microbial toxins, solvents) have considerable interferences in the health and well-being
of individuals. The liver is an extremely important organ in the body, responsible for
vascular, metabolic and secretory functions. In addition, it is also responsible for the
detoxification of all the chemical substances at which we are constantly exposed (not
only those ingested through diet and as a result of the environment interaction, but also
those resulting from endogenous metabolic processes, such as drugs and other cellular
metabolisms). It has been observed that the majority of subjects with C. albicans
overgrowth, present some problems in liver detoxification mechanisms. Moreover, the
presence of multiple chemical sensibilities and allergies is frequent in patients with
chronic candidiasis, which is a direct indicator of problems in detoxification reactions.
The damage of liver is an underlying factor in chronic candidiasis, as well as in chronic
fatigue, because when the liver is damaged by chemical toxins and others, the immune
function is severely compromised. Thus, enhanced liver function is vital, not only
23
before, but also during and even after procedures that destroy yeasts, in order to increase
the likelihood of success in candidiasis treatment [49,57,59,60,62].
Some procedures could help in the improvement of detoxification process by liver
(Table 3).
6.1.4. Natural anti-yeast agents
Natural anti-yeast agents with proven activity against C. albicans can be used to treat
the infection concomitantly to other procedures. Nevertheless, to be effective as primary
therapy, predisposing factors to chronic candidiasis, diet and lifestyle should also be
taken into account. The most studied compounds that act as natural agents against C.
albicans are caprylic acid; berberine-containing plants; probiotics; grapefruit seed
extract; garlic; tea tree oil; and enteric-coated volatile oil preparations containing
oregano, thyme, peppermint, and rosemary; propolis; ginger and cinnamon. However,
the occurrence of Herxheimer reaction is very frequent when an effective anti-yeast
therapy is used, due to the rapid elimination of the microorganisms, and subsequent
absorption of large amounts of yeast toxins, cell particles and antigens. The mentioned
reaction can be eliminated through supporting liver function, following dietary
recommendations and starting anti-yeast medications in low and gradually increasing
doses [49,57,59,60,97].
6.2. Therapeutic approach
In order to successively control the growth of C. albicans and related infections
(candidiasis), a therapeutic intervention is required.
24
After identification of the predisposing factors, it is essential to develop a diet to control
C. albicans growing. The most commonly used substances and phytotherapics in the
complementary treatment of candidiasis are presented in Table 4.
Besides the mentioned phytotherapics there are other plants with documented antifungal
activity, particularly against C. albicans, such as essential oils from ginger (Zingiber
officinale) [98–100], cassia (Cinnamomum cassia) [98,101] and others Cinnamomum
species [32,102], chamomile (Matricaria chamomilla) [57,103,104], lemon balm
(Melissa
officinalis)
[32,101,105],
thymus
(Thymus
vulgaris)
and
rosemary
(Rosmarinus officinalis) [101,106–109].
Nevertheless, there are still several unknown compounds from plants, that could act
synergistically, among themselves and with other natural compounds, against yeast
infections [57,59,60,97,110].
Other aspects should also be considered namely, rest and liquids intake mainly
vegetable diluted juices, soups and plant infusions. Moreover, it is necessary to promote
a positive mind and help patients to cope stress. Alcohol, simple sugars, tobacco and
cholesterol should be avoided due to their capacity of stimulating C. albicans
overgrowth, and impair the immune function. The support to thymus gland function is
also
provided
by
500
mg
of
crude
polypeptide
fractions,
twice
daily
[57,59,60,62,96,111].
The body ability to detoxify and eliminate some substances is mostly dependent of
healthy diet and lifestyle. As previously mentioned, liver is the responsible for the
detoxification of all chemical substances. Therefore, the optimization of liver function,
promoting their protection and using lipotropics factors, accelerates the elimination and
fat deposition in liver, and could offer significant benefits [57,59,60,97]. In some cases,
25
the use of formulas containing natural plant fibers derived from psyllium seed, kelp,
agar, pectin and plant gums, is necessary to help elimination of toxic substances and
protect the bowel wall from irritation. Moreover, these fiber formulas promote natural
bowel movements and, if anti-yeast therapies are employed, they guarantee that dead
yeast cells are excreted and not absorbed; 3-5 g of soluble fiber at bedtime are required
for the treatment of candidiasis [57,59,60,87,88,112,113].
The repair of intestinal flora is another crucial factor. Particularly, Lactobacilus
acidophilus, Bifidobacterium bifidum, Lactobacillus bulgaricus and Streptococcus
thermophilus are very important, not only as antifungals, antibacterials and antivirals,
but also in digestion and in production of vitamins and other substances important to
maintain gut and the all body healthy. The recommendation is a product containing 4-10
billion viable active organisms, 30 minutes after a meal. However, some foods, like
yogurt and kefir, could also be a good source of probiotics, but is necessary to take care,
mainly due to fact that the yogurt itself does not have the necessary amount of bacteria
and, in other hand, the presence of sugar promotes the overgrowth of C. albicans and
other microorganisms. Therefore, the yogurt should have the proper bacteria and should
not be sweetened [57,59,60,87,88,112,113].
Lastly, the use of nutritional supplements or herbs seems to be the best option to help
and control C. albicans overgrowth, and to promote a healthy bacterial flora. Antifungal
drugs should be prescribed only if necessary. In most cases, these therapeutic
interventions are effective to threat candidiasis, including chronic candidiasis. However,
if the patient cannot achieve a significant improvement and/or eradicate the infection, it
is necessary to perform a deeper evaluation [57,59,60,62]. If the organism is still
present, after repeat stool cultures and measure antigen levels, antibiotics could be
prescribed, combined with other recommendations [57,59,60]. Despite until now the
26
majority of studies focused essentially in the role of oils of plants, currently other
natural matrices preparations have been studied, namely, aqueous and alcoholic
extracts. It is very important to underline that the use of plants and other botanical
preparations are used, since ancient times, by primitive societies, due to healing
properties and therapeutic and psychotherapeutic benefits. It is important to address the
fact that plants are widely used to obtain a large variety of drugs, being used in folk
medicine for a long time [26–29,32–35]. Concerning that plants represent an economic,
easily and which are accessible for all of people, they can be used into a variety of
diseases, constituting an excellent source of biomolecules able to act like natural
antifungal agents and, at the same time, to encourage the search for other alternative
treatments. They can be used, both to complement a conventional treatment with
antifungal agents, and singly like a natural alternative treatment. In both situations, the
counseling and following of a growing control diet are crucial to ensure successful of
therapy.
Moreover, despite the increasing interest of several studies towards the identification of
several compounds with therapeutic potential and their synergistic effect, in
combination with other compounds, many properties of plants remain unknown, as well
as their main compounds. Thus, not only it is necessary to deepen the study of other
preparations of known plants but also investigate other therapeutic effects provided by
plants and the major responsible compounds.
7. Concluding remarks
All people are exposed to a variety of candidiasis predisposing factors, and some of
them are impossible to avoid. Candidiasis can affect different parts of the body (nails,
GI tract, and vagina, among others) being characterized by several symptoms, which
27
often-difficult diagnosis; additionally, the individual characteristics alter the
manifestation of signals and symptoms. As this infection is very uncomfortable and, in
some cases, offers a considerable health risk, the major and most important aspect is
prevention. Therefore, there are several aspects to consider and include in the daily
routine, which at first might seem insignificant, but that could provide a strength
protection.
To combat the infection different procedures are necessary according to the pathologic
conditions of the patient; if all daily care is considered, the probability of the infection
occurrence will be considerably reduced. However, in face of an infection, a rapid
intervention is necessary and, for this, other alternatives to antifungals and
antimicrobials are necessary.
Acknowledgements
The authors are grateful to Foundation for Science and Technology (FCT, Portugal) for
N. Martins grant (SFRH/BD/87658/2012), L. Barros researcher contract under
“Programa Compromisso com Ciência – 2008” and financial support to the research
center CIMO (strategic project PEst-OE/AGR/UI0690/2011).
References
1. Vázquez-González D, Perusquía-Ortiz AM, Hundeiker M, Bonifaz A. Opportunistic
yeast infections: candidiasis, cryptococcosis, trichosporonosis and geotrichosis. J. Ger.
Soc. Dermatology [Internet]. 2013 [cited 2013 May 27];11:381–94. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/23621330
2. McCullough MJ, Ross BC, Reade PC. Candida albicans: a review of its history,
taxonomy, epidemiology, virulence attributes, and methods of strain differentiation. Int.
J. Oral Maxillofac. Surg. [Internet]. 1996;25:136–44. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/8727588
3. Brunke S, Hube B. Two unlike cousins: Candida albicans and C. glabrata infection
strategies. Cell. Microbiol. [Internet]. 2013 [cited 2013 May 27];15:701–8. Available
from:
28
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3654559&tool=pmcentrez&
rendertype=abstract
4. Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, Schaller M, et al. Candida
albicans-epithelial interactions: dissecting the roles of active penetration, induced
endocytosis and host factors on the infection process. PLoS One [Internet]. 2012 [cited
2013 May 27];7:1–10. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3351431&tool=pmcentrez&
rendertype=abstract
5. Greenberg MS, Glick M. Burket’s Oral Medicine: Diagnosis and Treatment. 10
Edition. USA: BC Decker Inc.; 2003. p. 658 p.
6. Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in
critically ill non-immunosuppressed patients. Lancet Infect. Dis. 2003;3:685–702.
7. Abi-Said D, Anaissie E, Uzun O, Raad I, Pinzcowski H, Vartivarian S. The
epidemiology of hematogenous candidiasis caused by different Candida species. Clin.
Infect. Dis. [Internet]. 1997;24:1122–8. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/9195068
8. Raman SB, Nguyen MH, Cheng S, Badrane H, Iczkowski KA, Wegener M, et al. A
competitive infection model of hematogenously disseminated candidiasis in mice
redefines the role of Candida albicans IRS4 in pathogenesis. Infect. Immun. [Internet].
2013 [cited 2013 May 27];81:1430–8. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/23429534
9. Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms.
Virulence [Internet]. 2013;4:119–28. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3654610&tool=pmcentrez&
rendertype=abstract
10. Tsai P-W, Chen Y-T, Hsu P-C, Lan C-Y. Study of Candida albicans and its
interactions with the host: a mini review. BioMedicine [Internet]. Elsevier Taiwan LLC;
2013 [cited 2013 Aug 6];3:51–64. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S2211802012000824
11. Li SY, Yang YL, Chen KW, Cheng HH, Chiou CS, Wang TH, et al. Molecular
epidemiology of long-term colonization of Candida albicans strains from HIV-infected
patients. Epidemiol. Infect. [Internet]. 2006 [cited 2013 May 27];134:265–9. Available
from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2870383&tool=pmcentrez&
rendertype=abstract
12. Fanello S, Bouchara JP, Jousset N, Delbos V, LeFlohic AM. Nosocomial Candida
albicans acquisition in a geriatric unit: epidemiology and evidence for person-to-person
transmission. J. Hosp. Infect. [Internet]. 2001 [cited 2013 May 27];47:46–52. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/11161898
13. Kim J, Sudbery P. Candida albicans, a major human fungal pathogen. J. Microbiol.
[Internet]. 2011 [cited 2013 Aug 6];49:171–7. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/21538235
14. Department of Surgical Education ORMC. Management of Candida infections in
surgical patients. 2002. p. 1–10.
29
15. Silva S, Henriques M, Hayes A, Oliveira R, Azeredo J, Williams DW. Candida
glabrata and Candida albicans co-infection of an in vitro oral epithelium. J. oral Pathol.
Med. [Internet]. 2011 [cited 2013 May 27];40:421–7. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/21158929
16. McCullough MJ, Clemons K V., Stevens DA. Molecular epidemiology of the global
and temporal diversity of Candida albicans. Clin. Infect. Dis. [Internet]. 1999;29:1220–
5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10524966
17. Develoux M, Bretagne S. Candidoses et levuroses diverses. EMC - Mal. Infect.
[Internet]. 2005 [cited 2013 Aug 6];2:119–39. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S1638623X05000053
18. Lott TJ, Fundyga RE, Kuykendall RJ, Arnold J. The human commensal yeast,
Candida albicans, has an ancient origin. Fungal Genet. Biol. [Internet]. 2005 [cited 2013
Aug 6];42:444–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15809008
19. Uppuluri P, Chaturvedi AK, Srinivasan A, Banerjee M, Ramasubramaniam AK,
Köhler JR, et al. Dispersion as an important step in the Candida albicans biofilm
developmental cycle. PLoS Pathog. [Internet]. 2010 [cited 2013 Mar 10];6:1–13.
Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2847914&tool=pmcentrez&
rendertype=abstract
20. Silva S, Henriques M, Oliveira R, Williams D, Azeredo J. In vitro biofilm activity
of non-Candida albicans Candida species. Curr. Microbiol. [Internet]. 2010 [cited 2013
May 29];61:534–40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20401483
21. Sardi JCO, Scorzoni L, Bernardi T, Fusco-Almeida a M, Mendes Giannini MJS.
Candida species: current epidemiology, pathogenicity, biofilm formation, natural
antifungal products and new therapeutic options. J. Med. Microbiol. [Internet]. 2013
[cited 2013 Mar 5];62:10–24. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/23180477
22. Ferreira AV, Prado CG, Carvalho RR, Dias KST, Dias ALT. Candida albicans and
non-C. albicans Candida species: comparison of biofilm production and metabolic
activity in biofilms, and putative virulence properties of isolates from hospital
environments and infections. Mycopathologia [Internet]. 2013 [cited 2013 May
27];175:265–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23532754
23. González ID-C, González FG-B, Cuesta TS, Fernández JM, Rodríguez JMD-A,
Ferrairo RAE, et al. Patient preferences and treatment safety for uncomplicated
vulvovaginal candidiasis in primary health care. BMC Public Health [Internet]. BioMed
Central Ltd; 2011 [cited 2013 May 29];11:1–8. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3048533&tool=pmcentrez&
rendertype=abstract
24. Sanglard D, Odds FC. Reviews resistance of Candida species to antifungal agents:
molecular mechanisms and clinical consequences. Lancet Infect. Dis. 2002;2:73–85.
25. Kanafani ZA, Perfect JR. Resistance to antifungal agents: mechanisms and clinical
impact. Clin. Infect. Dis. - Antimicrob. Resist. [Internet]. 2008 [cited 2013 May
21];46:120–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18171227
26. Alves-Silva JM, Santos SMD dos, Pintado ME, Pérez-Álvarez JA, Fernández-López
J, Viuda-Martos M. Chemical composition and in vitro antimicrobial, antifungal and
30
antioxidant properties of essential oils obtained from some herbs widely used in
Portugal. Food Control [Internet]. Elsevier Ltd; 2013 [cited 2013 Jun 24];32:371–8.
Available from: http://linkinghub.elsevier.com/retrieve/pii/S0956713513000030
27. Silva F, Ferreira S, Duarte A, Mendonça DI, Domingues FC. Antifungal activity of
Coriandrum sativum essential oil, its mode of action against Candida species and
potential synergism with amphotericin B. Phytomedicine [Internet]. 2011 [cited 2013
Mar 13];19:42–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21788125
28. Rana IS, Rana AS, Rajak RC. Evaluation of antifungal activity in essential oil of the
Syzygium aromaticum (L.) by extration, purification and analysis of its main
component eugenol. Brazilian J. Microbiol. 2011;42:1269–77.
29. Agarwal V, Lal P, Pruthi V. Effect of plant oils on Candida albicans. J. Microbiol.
Immunol. Infect. [Internet]. Taiwan Society of Microbiology; 2010 [cited 2013 Aug
6];43:447–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21075713
30. Asl MN, Hosseinzadeh H. Review of pharmacological effects of Glycyrrhiza sp .
and its bioactive compounds. Phyther. Res. 2008;22:709–24.
31. Shojaii A, Abdollahi Fard M. Review of pharmacological properties and chemical
constituents of Pimpinella anisum. Int. Sch. Res. Netw. - ISRN Pharm. [Internet]. 2012
[cited 2013 Mar 12];2012:1–8. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3405664&tool=pmcentrez&
rendertype=abstract
32. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils
- A review. Food Chem. Toxicol. [Internet]. 2008;46:446–75. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/17996351
33. Singh A, Duggal S, Kaur N, Singh J. Berberine: Alkaloid with wide spectrum of
pharmacological activities. J. Nat. Prod. 2010;3:64–75.
34. Asgarpanah J, Kazemivash N. Phytochemistry, pharmacology and medicinal
properties of Coriandrum sativum L. African J. Pharm. Pharmacol. [Internet]. 2012
[cited 2013 Mar 20];6:2340–5. Available from:
http://www.academicjournals.org/AJPP/abstracts/abstracts/abstract
2012/22Aug/Asgarpanah and Kazemivash.htm
35. Sher A. Antimicrobial activity of natural products from medicinal plants. Gomal J.
Med. Sci. 2009;7:72–8.
36. Lewis LE, Bain JM, Lowes C, Gow NAR, Erwig L-P. Candida albicans infection
inhibits macrophage cell division and proliferation. Fungal Genet. Biol. [Internet].
Elsevier Inc.; 2012 [cited 2013 May 27];49:679–80. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3430961&tool=pmcentrez&
rendertype=abstract
37. Kwamin F, Nartey NO, Codjoe FS, Newman MJ. Distribution of Candida species
among HIV-positive patients with oropharyngeal candidiasis in Accra , Ghana. J. Infect.
Dev. Ctries. 2013;7:041–5.
38. Westwater C, Schofield DA, Nicholas PJ, Paulling EE, Balish E. Candida glabrata
and Candida albicans; dissimilar tissue tropism and infectivity in a gnotobiotic model of
mucosal candidiasis. FEMS Immunol. Med. Microbiol. [Internet]. 2007 [cited 2013
May 27];51:134–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17854475
31
39. Sullivan DJ, Moran GP, Pinjon E, Almosaid A, Stokes C, Vaughan C, et al.
Comparison of the epidemiology, drug resistance mechanisms, and virulence of
Candida dubliniensis and Candida albicans. FEMS Yeast Res. [Internet]. 2004 [cited
2013 May 27];4:369–76. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S156713560300240X
40. Epstein JB, Polsky B. Oropharyngeal candidiasis: a review of its clinical spectrum
and current therapies. Clin. Ther. [Internet]. 1998;20:40–57. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/9522103
41. Calderone RA, Fonzi WA. Virulence factors of Candida albicans. Trends Microbiol.
[Internet]. 2001;9:327–35. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/11435107
42. Sobel JD. Vulvovaginal candidosis. Lancet [Internet]. 2007;369:1961–71. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/17560449
43. Rad MM, Zafarghandi S, Abbasabadi B, Tavallaee M. The epidemiology of
Candida species associated with vulvovaginal candidiasis in an Iranian patient
population. Eur. J. Obstet. Gynecol. Reprod. Biol. [Internet]. Elsevier Ireland Ltd; 2011
[cited 2013 May 27];155:199–203. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/21194828
44. Tarry W, Fisher M, Shen S, Mawhinney M. Candida albicans: the estrogen target
for vaginal colonization. J. Surg. Res. [Internet]. 2005 [cited 2013 Aug 6];129:278–82.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16111702
45. Geiger AM, Foxman B, Sobel JD. Chronic vulvovaginal candidiasis: characteristics
of women with Candida albicans, C. glabrata and no Candida. Genitourin. Med.
[Internet]. 1995;71:304–7. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1195546&tool=pmcentrez&
rendertype=abstract
46. Ahmad A, Khan AU. Prevalence of Candida species and potential risk factors for
vulvovaginal candidiasis in Aligarh, India. Eur. J. Obstet. Gynecol. Reprod. Biol.
[Internet]. 2009 [cited 2013 May 27];144:68–71. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/19261369
47. Liu XP, Fan SR, Bai FY, Li J, Liao QP. Antifungal susceptibility and genotypes of
Candida albicans strains from patients with vulvovaginal candidiasis. Mycoses
[Internet]. 2009 [cited 2013 May 27];52:24–8. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/18498300
48. David LM, Walzman M, Rajamanoharan S. Genital colonisation and infection with
candida in heterosexual and homosexual males. Genitourin. Med. [Internet].
1997;73:394–6. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1195901&tool=pmcentrez&
rendertype=abstract
49. Longe JL. The Gale Encyclopedia of Alternative Medicine. 2nd ed. Deirdre S.
Blanchfield, Laurie Fundukian E, Watts, editors. Thomson GALE; 2005.
50. McGirt LY, Martins CR. Dermatologic diagnoses in the perianal area. Clin. Colon
Rectal Surg. [Internet]. 2004;17:241–5. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2780053&tool=pmcentrez&
rendertype=abstract
32
51. Wet PM de, Rode H, Dyk A Van, Millar AJW. Candidiasis perianal-estudio
comparativo de mupirocina y nistatina. Int. J. Dermatol. 1999;38:618–22.
52. Mårdh P-A, Novikova N, Stukalova E. Colonisation of extragenital sites by Candida
in women with recurrent vulvovaginal candidosis. BJOG [Internet]. 2003;110:934–7.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/14550364
53. Okada M, Hisajima T, Ishibashi H, Miyasaka T, Abe S, Satoh T. Pathological
analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis
model in the early infection stage. Arch. Oral Biol. [Internet]. Elsevier Ltd; 2013 [cited
2013 May 27];58:444–50. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/23092606
54. Dronda F, Alonso-Sanz M, Laguna F, Chaves F, Martínez-Suárez J V., RodríguezTudela JL, et al. Mixed oropharyngeal candidiasis due to Candida albicans and nonalbicans Candida strains in HIV-infected patients. Eur. J. Clin. Microbiol. Infect. Dis.
[Internet]. 1996;15:446–52. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/8839637
55. Jin Y, Samaranayake LP, Samaranayake Y, Yip HK. Biofilm formation of Candida
albicans is variably affected by saliva and dietary sugars. Arch. Oral Biol. [Internet].
2004 [cited 2013 Aug 6];49:789–98. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/15308423
56. Asmundsdóttir LR, Erlendsdóttir H, Agnarsson BA, Gottfredsson M. The
importance of strain variation in virulence of Candida dubliniensis and Candida
albicans: results of a blinded histopathological study of invasive candidiasis. Clin.
Microbiol. Infect. [Internet]. 2009;15:576–85. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/19604278
57. Murray MT, Pizzorno J. Enciclopedia de Medicina Natural. 2a Edicion. Domingo J,
editor. Espanha: Ediciones Tutor S.A.; 1998. p. 638 p.
58. Rubinstein E, Mark Z, Haspel J, Ben-Ari G, Dreznik Z, Mirelman D, et al.
Antibacterial activity of the pancreatic fluid. Gastroenterology. 1989;88:927–32.
59. Balch PA. Prescription for Nutritional Healing. Fourth Edi. Avery, editor. London,
England: Penguin Group; 2006. p. 869 p.
60. Balch JF, Stengler M. Prescription for Natural Cures. John Wiley & Sons I, editor.
New Jersey; 2004. p. 724 p.
61. Brock JH. Lactoferrin in human milk: its role in iron absorption and protection
against enteric infection in the newborn infant. Arch. Dis. Child. [Internet].
1980;55:417–21. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1626933&tool=pmcentrez&
rendertype=abstract
62. Pizzorno Jr. JE, Murray MT, Joiner-Bey H. Manual de Medicina Natural: Toma de
decisiones en la clinica. 2nd Editio. Elsevier, editor. Barcelona - Espanha: Churchill
Livingstone; 2009. p. 824 p.
63. Serrano R, Bernal D, Simón E, Ariño J. Copper and iron are the limiting factors for
growth of the yeast Saccharomyces cerevisiae in an alkaline environment. J. Biol.
Chem. [Internet]. 2004 [cited 2013 May 23];279:19698–704. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/14993228
33
64. Pas M, Piskur B, Sustaric M, Raspor P. Iron enriched yeast biomass--a promising
mineral feed supplement. Bioresour. Technol. [Internet]. 2007 [cited 2013 Jul
18];98:1622–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16935492
65. Prevorovský M, Stanurová J, Půta F, Folk P. High environmental iron
concentrations stimulate adhesion and invasive growth of Schizosaccharomyces pombe.
FEMS Microbiol. Lett. [Internet]. 2009 [cited 2013 Jul 18];293:130–4. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/19222572
66. Lan C-Y, Rodarte G, Murillo LA, Jones T, Davis RW, Dungan J, et al. Regulatory
networks affected by iron availability in Candida albicans. Mol. Microbiol. [Internet].
2004 [cited 2013 Jul 18];53:1451–69. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/15387822
67. Schenkels LCPM, Veerman ECI, Amerongen AVN. Biochemical Composition of
Human Saliva in Relation To Other Mucosal Fluids. Crit. Rev. Oral Biol. Med.
[Internet]. 1995 [cited 2013 Aug 7];6:161–75. Available from:
http://cro.sagepub.com/cgi/doi/10.1177/10454411950060020501
68. Kim J, Han BJ, Kim H, Lee JY, Joo I, Omer S, et al. Th1 immunity induction by
ginsenoside Re involves in protection of mice against disseminated candidiasis due to
Candida albicans. Int. Immunopharmacol. [Internet]. Elsevier B.V.; 2012 [cited 2013
May 27];14:481–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22940185
69. Blanco JL, Garcia ME. Immune response to fungal infections. Vet. Immunol.
Immunopathol. [Internet]. 2008 [cited 2013 Aug 6];125:47–70. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/18565595
70. Eggimann P, Garbino J, Pittet D. Management of Candida species infections in
critically ill patients. Lancet Infect. Dis. 2003;3:772–85.
71. Chi H-W, Yang Y-S, Shang S-T, Chen K-H, Yeh K-M, Chang F-Y, et al. Candida
albicans versus non-albicans bloodstream infections: the comparison of risk factors and
outcome. J. Microbiol. Immunol. Infect. [Internet]. Elsevier Taiwan LLC; 2011 [cited
2013 May 27];44:369–75. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/21524971
72. Wroblewska MM, Swoboda-Kopec E, Rokosz A, Krawczyk E, Marchel H, Luczak
M. Epidemiology of clinical isolates of Candida albicans and their susceptibility to
triazoles. Int. J. Antimicrob. Agents [Internet]. 2002;20:472–5. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/12458145
73. Abe F, Katoh T, Inaba H, Hotchi M. Experimental candidiasis associated with liver
injury - Role of transferrin. Mycopathologia. 1988;104:3–6.
74. Abe F, Nagata S, Hotchi M. Experimental candidiasis in liver injury.
Mycopathologia [Internet]. 1987;100:37–42. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/2975353
75. Katiraee F, Khosravi AR, Khalaj V, Hajiabdolbaghi M, Khaksar A, Rasoolinejad M,
et al. Oropharyngeal candidiasis and oral yeast colonization in Iranian Human
Immunodeficiency Virus positive patients. J. Mycol. Med. [Internet]. Elsevier Masson
SAS; 2010 [cited 2013 Aug 6];20:8–14. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S1156523309001164
34
76. Kontoyiannis DP, Lewis RE. Antifungal drug resistance of pathogenic fungi. Lancet
[Internet]. 2002;359:1135–44. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/11943280
77. Gerard R, Sendid B, Colombel JF, Poulain D, Jouault T. An immunological link
between Candida albicans colonization and Crohn’s disease. Crit. Rev. Microbiol.
2013;1–5.
78. Kumamoto CA. Inflammation and gastrointestinal Candida colonization. Curr.
Opin. Microbiol. [Internet]. Elsevier Ltd; 2011 [cited 2013 Aug 8];14:386–91.
Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3163673&tool=pmcentrez&
rendertype=abstract
79. Trojanowska D, Zwolinska-Wcislo M, Tokarczyk M, Kosowski K, Mach T, Budak
A. The role of Candida in inflammatory bowel disease. Estimation of transmission of C.
albicans fungi in gastrointestinal tract based on genetic affinity between strains. Int.
Med. J. Exp. Clin. Res. 2010;16:451–7.
80. García-Ruiz JC, Amutio E, Ponton J. Infección fúngica invasora en pacientes
inmunodeficientes. Rev. Iberoam. Micol. 2004;21:55–62.
81. Jawhara S, Thuru X, Standaert-Vitse A, Jouault T, Mordon S, Sendid B, et al.
Colonization of mice by Candida albicans is promoted by chemically induced colitis
and augments inflammatory responses through galectin-3. J. Infect. Dis. [Internet]. 2008
[cited 2013 Aug 8];197:972–80. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/18419533
82. Standaert-Vitse A, Jouault T, Vandewalle P, Mille C, Seddik M, Sendid B, et al.
Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibody markers
of Crohn’s disease. Gastroenterology [Internet]. 2006 [cited 2013 Aug 8];130:1764–75.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16697740
83. Sendid B, Jouault T, Vitse A, Fradin C, Colombel JF, Poulain D. Glycannes
pariétaux de levures et anticorps spécifiques. MS Med. Sci. 2009;25:473–81.
84. Rehaume LM, Jouault T, Chamaillard M. Lessons from the inflammasome: a
molecular sentry linking Candida and Crohn’s disease. Trends Immunol. [Internet].
Elsevier Ltd; 2010 [cited 2013 Aug 8];31:171–5. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/20149741
85. Gerard R, Sendid B, Techy A, Vernier-Massouille G, Jouault T, Francois N, et al.
Candida albicans colonization and anti-glycan antibodies in active and quiescent
Crohn’s disease [Internet]. J. Crohn’s Colitis. European’s Crohn's and Colitis
Organisation; 2013 Feb p. S290–S291. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S1873994613607187
86. McKenzie H, Main J, Pennington CR, Parratt D. Antibody to selected strains of
Saccharomyces cerevisiae (baker’s and brewer's yeast) and Candida albicans in Crohn's
disease. Gut [Internet]. 1990;31:536–8. Available from:
http://gut.bmj.com/cgi/doi/10.1136/gut.31.5.536
87. García-elorriaga G, Rey-pineda G. Nutrition and intestinal microflora. J. Nutr. Ther.
2013;2:112–21.
35
88. Isolauri E, Kirjavainen P V., Salminen S. Probiotics: a role in the treatment of
intestinal infection and inflammation? Gut [Internet]. 2002;50:54–9. Available from:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1867676&tool=pmcentrez&
rendertype=abstract
89. Diagnostics G. Diagnostic Laboratory Testing for Wellness & Preventive Medicine
[Internet]. 2013. [cited 2013 Aug 19]. Available from:
http://www.gdx.net/product/10006
90. Tamura NK, Negri MFN, Bonassoli LA, Svidzinski TIE. Virulence factors for
Candida spp recovered from intravascular catheters and hospital workers ’ hands. Rev.
Soc. Bras. Med. Trop. 2007;40:91–3.
91. Birmingham N, Payankaulam S, Thanesvorakul S, Stefura B, HayGlass K, Gangur
V. An ELISA-based method for measurement of food-specific IgE antibody in mouse
serum: an alternative to the passive cutaneous anaphylaxis assay. J. Immunol. Methods
[Internet]. 2003 [cited 2013 Aug 9];275:89–98. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S0022175903000085
92. Schubert-Ullrich P, Rudolf J, Ansari P, Galler B, Führer M, Molinelli A, et al.
Commercialized rapid immunoanalytical tests for determination of allergenic food
proteins: an overview. Anal. Bioanal. Chem. [Internet]. 2009 [cited 2013 Aug
9];395:69–81. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19308361
93. Ladics GS. Current codex guidelines for assessment of potential protein
allergenicity. Food Chem. Toxicol. [Internet]. Elsevier Ltd; 2008 [cited 2013 Aug 9];46
Suppl 1:20–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18708115
94. Landschoot A Van. Gluten-free barley malt beers. Cerevisia [Internet]. Elsevier
B.V.; 2011 [cited 2013 Aug 9];36:93–7. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S137371631100117X
95. Foster AP, Knowles TG, Moore AH, Cousins PDG, Day MJ, Hall EJ. Serum IgE
and IgG responses to food antigens in normal and atopic dogs, and dogs with
gastrointestinal disease. Vet. Immunol. Immunopathol. [Internet]. 2003 [cited 2013 Aug
9];92:113–24. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S0165242703000333
96. Shahar E, Kriboy N, Pollack S. White cell enhancement in the treatment of severe
candidosis. Lancet. 1995;346:974–5.
97. Murray MT, Pizzorno J. The Encyclopedia of healing foods. Atria Book. New York,
NY; 2005. p. 912 p.
98. Almeida L de FD, Cavalcanti YW, Viana WP, Lima E de O. Screening da Atividade
Antifúngica de Óleos Essenciais sobre Candida Albicans. Rev. Bras. Ciências da Saude.
2011;14:51–6.
99. Jantar I bin, Yassin MSM, Chin CB, Chen LL, Sim NL. Antifungal activity of the
essential oils of nine Zingiberaceae species. Pharm. Biol. 2003;41:392–7.
100. Joe MM, Jayachitra J, Vijayapriya M. Antimicrobial activity of some common
spices against certain human pathogens. J. Med. Plants Res. 2009;3:1134–6.
101. Taguchi Y, Takizawa T, Ishibashi H, Sagawa T, Arai R, Inoue S, et al. Therapeutic
effects on murine oral candidiasis by oral administration of cassia (Cinnamomum
36
cassia) preparation. Nihon Ishinkin Gakkai Zasshi [Internet]. 2010;51:13–21. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/20185867
102. Höferl M, Buchbauer G, Jirovetz L, Schmidt E, Stoyanova A, Denkova Z, et al.
Correlation of Antimicrobial Activities of Various Essential Oils and Their Main
Aromatic Volatile Constituents. J. Essenc. oil Res. 2009;21:459–64.
103. Roby MHH, Sarhan MA, Selim KA-H, Khalel KI. Antioxidant and antimicrobial
activities of essential oil and extracts of fennel (Foeniculum vulgare L.) and chamomile
(Matricaria chamomilla L.). Ind. Crops Prod. [Internet]. Elsevier B.V.; 2013 [cited 2013
Oct 7];44:437–45. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S092666901200564X
104. Bail S, Buchbauer G, Jirovetz L, Denkova Z, Slavchev A, Stoyanova A, et al.
Antimicrobial Activities of Roman Chamomile Oil From France and Its Main
Compounds. J. Essent. oil Res. 2009;21:283–7.
105. Ertürk Ö. Antibacterial and antifungal activity of ethanolic extracts from eleven
spice plants. Biologia (Bratisl). [Internet]. 2006 [cited 2013 Oct 4];61:275–8. Available
from: http://www.springerlink.com/index/10.2478/s11756-006-0050-8
106. Bozin B, Mimica-Dukic N, Samojlik I, Jovin E. Antimicrobial and antioxidant
properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L.,
Lamiaceae) essential oils. J. Agric. Food Chem. [Internet]. 2007;55:7879–85. Available
from: http://www.ncbi.nlm.nih.gov/pubmed/17708648
107. Carretto C de FP, Navas EAF de A, Paradella TC, Oliveira LD de, Junqueira JC,
Jorge AOC. Efeitos do chá de tomilho sobre a aderência in vitro de Streptococcus
mutans ao esmalte dentário e Candida albicans à resina acrílica. Rev. Oncol. da UNESP.
2007;36:281–6.
108. Abdul BA, Hassan AM, Hassan AS. In vitro antimicrobial activity of Thymus
vulgaris, Origanum vulgare and Rosmarinus officinalis against dental caries pathogens.
Haitham J. Pure Appl. Sci. 2012;25:1–7.
109. Van Vuuren SF, Suliman S, Viljoen AM. The antimicrobial activity of four
commercial essential oils in combination with conventional antimicrobials. Lett. Appl.
Microbiol. [Internet]. 2009 [cited 2013 Mar 9];48:440–6. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/19187494
110. Murray MT. The healing power of herbs. 2nd ed. Gramercy Books, editor. New
York, NY: Random House; 2004. p. 410 p.
111. Vanaclocha B, Cañigueral S. Fitoterapia: Vademecum de Prescripción. 4th ed.
Masson, editor. Barcelona; 2003. p. 1092 p.
112. Amara AA, Shibl A. Role of Probiotics in health improvement, infection control
and disease treatment and management. Saudi Pharm. J. [Internet]. King Saud
University; 2013 [cited 2013 Aug 7];1–8. Available from:
http://linkinghub.elsevier.com/retrieve/pii/S1319016413000819
113. Kaur IP, Kuhad A, Garg A, Chopra K. Probiotics: delineation of prophylactic and
therapeutic benefits. J. Med. Food [Internet]. 2009 [cited 2013 Aug 8];12:219–35.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/19459724
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38
Predisposing factors
Decreased digestive secretions
Dietary factors and nutrients deficiency
Impaired immune system and
underlying disease states
Impaired liver function
Drugs and prolonged use of antibiotics
Altered bowel flora
Prolonged antibiotic use
Prevention
Personal hygiene
Dietary factors
Immune system
Candidiasis classes
Diagnosis
Genital candidiasis
Intrauterine candidiasis
Anal candidiasis
Nails candidiasis
Oral candidiasis
Signals
Symptoms
Diagnosis methods
Alternative treatment
Diet and nutrition
Enhancing immune system
Detoxification
Natural anti-yeast agents
Therapeutical approach
Figure 1. Representative scheme of interactions between the main variables related to
candidiasis.
39
Table 1. Main general guidelines for personal hygiene [49,59,60,62]
Superficial infections
Vaginal candidiasis
Personal belongings
Procedures
Avoid contact with other body parts, as well as with other
persons
Maintain the skin clean and dry
During menstruation, compresses without cosmetic
products should be used
Avoid frequent use of vaginal douches and intimate
hygiene products (they alter the normal vaginal pH,
causing unbalance and favoring the onset of infection)
Maintain external vaginal area completely dry
Avoid prolonged use of bathing suit or damp or wet
underwear
The act of cleaning up should always be done backward
Avoid sexual relations during antifungal therapy
Bed linen, bathroom and personal clothing should be
washed with very hot water, separated from the others at
home and disinfected after use
Avoid tight clothing and use cotton underwear
40
Table 2. Dietary considerations in the treatment of candidiasis [57,59,60,62,97]
Food characteristics
Refined carbohydrate sources
Fungi and/or yeast sources
To avoid
Lactose and antibiotic sources
Allergenic foods
To limit
Carbohydrate sources
Vitamin sources
To consume
Protein sources
Fiber sources
Food products
Refined sugars (sucrose, fructose, corn
syrup), fruit juice, honey, maple syrup
Alcoholic beverages, dried fruits,
cheeses, peanut
Dairy products
Dairy products, eggs, chocolate, fried
and processed foods, wheat, peanuts
Corn and potatoes
Vegetables, fruits (apples, pears,
cranberries, cherries, blueberries and
other soft fruit)
Fish, meat and biological poultry
Whole grains, ground flaxseeds
41
Table 3. Procedures to improve liver function and detoxification [49,57,59,60,97]
Procedures
Consuming garlic, onions, chlorella, spirulina, wheatgrass;
Diet based on fresh fruits and vegetables, whole grains,
legumes, nuts and seeds;
Improve liver function Avoiding alcohol and adopt others healthy lifestyles;
Supplementation with a high-potency multiple vitamin and
minerals;
Regular exercise
Diet based on high-fiber plant foods to supplying a high
amount of dietary fiber;
If necessary, prescribed additional fiber formulas- 3 to 5 g of
soluble fiber at the bedtime- composed by natural plant fibers,
Improve detoxification
derived from psyllium seed, kelp, agar, pectin, guar, and
others that promote a natural mechanism of bowel movement;
Using lipotropic formulas* such as choline, betaine and
methionine or cysteine, silimarin to protect the liver
*
The importance of lipotropic factors is related to increased levels of two important liver
substances: SAMs (S-adenosylmethionine) and glutathione, that are the major lipotropic
and detoxifying compounds in the liver, respectively.
42
Table 4. Substances and phytochemicals commonly used in alternative treatment of
candidiasis
Substance
Dosage/Description
High-potency complex of multivitamins Hypoallergenic formulas, free of yeasts
and minerals formula
Zinc picolinate
45 mg/day
Selenium
200 µg/day
Caprylic acid
Formula of slow liberation (1 g with meals)
Probiotics (intestinal flora)
Products containing Lactobacillus
Fiber supplement
Guar gum, pectin or psyllium seeds (1
teaspoon before bedtime)
Phytotherapics
Dosage/Description
Tabebuia impetiginosa (lapacho)
15-20 g of bark in 0.5 L boiling water for 515 minutes, 3-4 times/day;
Berberis vulgaris (barberry)
The following doses, 3 times/day:
Dried bark of the root (as tea): 1-2 g
Tincture (1:5): 4-6 mL (1-1 and ½ teaspoon)
Liquid extract (1:1): 0.5-2 mL (¼-½
teaspoon)
Powdered solid extract (4:1): 250-500 mg
Hydrastis Canadensis (goldenseal)
The following doses, 3 times/day:
Dried root (as tea): 1-2 g
Tincture (1:5): 4-6 mL (1-1 and ½ teaspoon)
Liquid extract (1:1): 0.5-2 mL (¼-½
teaspoon)
Powdered solid extract (4:1): 250-500 mg
Origanum vulgare (oregano) oil
300-500 mg by capsule or liquid form, 3
times/day, with meals to avoid digestive
unease
Allium sativum (garlic)
Actual guidelines based on allin (10 mg) and
allicin (4000 µg), which is equivalent to 4000
mg of fresh garlic or 500-1000 mg of aged
garlic
Citrus paradise (grapefruit) seed extract 200 mg, 2-3 times/day
43